The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption

Laura M. Saba, Stephen C. Flink, Lauren A. Vanderlinden, Yedy Israel, Lutske Tampier, Giancarlo Colombo, Kalervo Kiianmaa, Richard Bell, Morton P. Printz, Pamela Flodman, George Koob, Heather N. Richardson, Joseph Lombardo, Paula L. Hoffman, Boris Tabakoff

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

A quantitative genetic approach, which involves correlation of transcriptional networks with the phenotype in a recombinant inbred (RI) population and in selectively bred lines of rats, and determination of coinciding quantitative trait loci for gene expression and the trait of interest, has been applied in the present study. In this analysis, a novel approach was used that combined DNA-Seq data, data from brain exon array analysis of HXB/BXH RI rat strains and six pairs of rat lines selectively bred for high and low alcohol preference, and RNA-Seq data (including rat brain transcriptome reconstruction) to quantify transcript expression levels, generate co-expression modules and identify biological functions that contribute to the predisposition of consuming varying amounts of alcohol. A gene co-expression module was identified in the RI rat strains that contained both annotated and unannotated transcripts expressed in the brain, and was associated with alcohol consumption in the RI panel. This module was found to be enriched with differentially expressed genes from the selected lines of rats. The candidate genes within the module and differentially expressed genes between high and low drinking selected lines were associated with glia (microglia and astrocytes) and could be categorized as being related to immune function, energy metabolism and calcium homeostasis, as well as glial-neuronal communication. The results of the present study show that there are multiple combinations of genetic factors that can produce the same phenotypic outcome. Although no single gene accounts for predisposition to a particular level of alcohol consumption in every animal model, coordinated differential expression of subsets of genes in the identified pathways produce similar phenotypic outcomes. Database The datasets supporting the results of the present study are available at http://phenogen.ucdenver.edu Using a

Original languageEnglish
Pages (from-to)3556-3578
Number of pages23
JournalFEBS Journal
Volume282
Issue number18
DOIs
StatePublished - Sep 1 2015

Fingerprint

Transcriptome
Alcohol Drinking
Rats
Brain
Genes
Alcohols
Inbred Strains Rats
Gene Regulatory Networks
Gene Expression
Neuroglia
Quantitative Trait Loci
Microglia
Astrocytes
Energy Metabolism
Drinking
Exons
Homeostasis
Animal Models
Communication
Databases

Keywords

  • alcohol consumption
  • gene expression
  • HXB RI rat strains
  • neuroinflammation
  • rat selected lines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Saba, L. M., Flink, S. C., Vanderlinden, L. A., Israel, Y., Tampier, L., Colombo, G., ... Tabakoff, B. (2015). The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption. FEBS Journal, 282(18), 3556-3578. https://doi.org/10.1111/febs.13358

The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption. / Saba, Laura M.; Flink, Stephen C.; Vanderlinden, Lauren A.; Israel, Yedy; Tampier, Lutske; Colombo, Giancarlo; Kiianmaa, Kalervo; Bell, Richard; Printz, Morton P.; Flodman, Pamela; Koob, George; Richardson, Heather N.; Lombardo, Joseph; Hoffman, Paula L.; Tabakoff, Boris.

In: FEBS Journal, Vol. 282, No. 18, 01.09.2015, p. 3556-3578.

Research output: Contribution to journalArticle

Saba, LM, Flink, SC, Vanderlinden, LA, Israel, Y, Tampier, L, Colombo, G, Kiianmaa, K, Bell, R, Printz, MP, Flodman, P, Koob, G, Richardson, HN, Lombardo, J, Hoffman, PL & Tabakoff, B 2015, 'The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption', FEBS Journal, vol. 282, no. 18, pp. 3556-3578. https://doi.org/10.1111/febs.13358
Saba LM, Flink SC, Vanderlinden LA, Israel Y, Tampier L, Colombo G et al. The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption. FEBS Journal. 2015 Sep 1;282(18):3556-3578. https://doi.org/10.1111/febs.13358
Saba, Laura M. ; Flink, Stephen C. ; Vanderlinden, Lauren A. ; Israel, Yedy ; Tampier, Lutske ; Colombo, Giancarlo ; Kiianmaa, Kalervo ; Bell, Richard ; Printz, Morton P. ; Flodman, Pamela ; Koob, George ; Richardson, Heather N. ; Lombardo, Joseph ; Hoffman, Paula L. ; Tabakoff, Boris. / The sequenced rat brain transcriptome - Its use in identifying networks predisposing alcohol consumption. In: FEBS Journal. 2015 ; Vol. 282, No. 18. pp. 3556-3578.
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